Typically, production of biologic material is accomplished through the use of bioreactor trains. These trains consist of multiple bioreactors that scale from small inoculation reactors up to full production volumes. These typical bioreactors are dimensioned such that liquid height is greater than vessel diameter; that is, typical bioreactors have a height to width aspect ratio that is greater than 1:1 however, at low volumes ( 1/20 of the working volume) typical reactors have a very low aspect ratio (liquid height to vessel width). These low aspect ratios are known to cause difficulties in sparging, mixing, and ultimately can lead to difficulties in cell growth and unwanted cell death. Typical bioreactors are designed and sized to scale up the volume of the culture from inoculum in progressively increasing volume seed reactors until sufficient culture volume for production of the desired product has been reached in the production bioreactor. Typically bioreactors are designed to be of fixed diameter and with dished heads and bottoms. The bioreactors are typically constructed with stainless steel tanks, but can also have a disposable liner, a disposable bag and the like.
As such, production scale bioreactor processing suffers from large bioreactor train footprints, high cleaning costs, unwanted lag time and lost seed time when switching between reactors in the train. Each seed bioreactor involves a transfer from one bioreactor to another and introduces the culture to conditions that differ from the end of the previous bioreactor. This typically produces a “lag phase” effect where the cell growth stalls for a period before attaining exponential growth again. For large scale, this typical processing requires multiple reactors resulting in increased facility footprint, and increased preparation activities resulting in increased production time and costs. For example, a 20,000 liter (L) desired production volume bioreactor train can consist of a 200 L inoculation bioreactor (designated N−3), followed by a 1000 L seed bioreactor (designated N−2), followed by a 5000 L seed bioreactor (designated N−1) and finally a 20,000 L volume bioreactor (designated N). This multi-reactor train leads to more clean-in-place (CIP) cycles and associated CIP systems, more steam-in-place (SIP), bioreactor start-up steps, increased draw on utilities (water, steam, waste), complicated plant scheduling and operational execution activities, and greater risk of contamination.
Therefore, improved production scale bioreactor processing devices, systems, and methods are desired.